Pancreatin is a mixture of enzymes obtained by extraction of the pancreas which consists essentially of lipase, amylase and protease. A more detailed definition of pancreatin can be found for example in the United States Pharmacopeia-The National Formulary 1990 (United States Pharmacopeial Convention, Inc., USP XXII, starting at page 1007). Pancreatin has a variety of uses including uses in human and veterinary medicine, wherein it can be used to correct digestive deficiencies.
Pancreatin which consists of dried defatted pancreas is prepared from fresh or frozen pancreas by methods which are aimed at preserving the enzymatic activities present in the pancreas. Although pancreas from different animal origin can be used as the starting material, porcine pancreas is usually preferred due to its higher amylolytic and lipolytic activities.
The numerous known methods for producing pancreatin usually involve a treatment of the pancreas through an autolysis, a degreasing and a drying step (Lewis, U.S. Pat. No. 3,956,483). The autolysis step is determinant in producing a pancreatin having high enzymatic activities, since enzymes present in the pancreas need to be converted from their inactive form to their activated form. For example, the pro-enzymes of the proteases present in a comminuted, frozen or thawed pancreas are activated by the addition of trypsin and enterokinase and incubation thereof in the presence of water, salt solutions, or solvents such as glycerin, 25% ethanol and 20% acetic acid (U.S. Pat. No. 4,019,958, Hell et al.). Precipitation with inorganic salts, organic solvents, or tannins followed by a drying step are most generally performed on such extracts.
One particular method of autolysing a pancreas preparation is that of Schultze (U.S. Pat. No. 4,623,624) which teaches the use of isopropanol or acetone therefor and the obtention of a pancreatin preparation having a low germ count due to the isopropanol treatment. Unfortunately, the method also encompasses the use of high concentration and hence large volumes of isopropanol to stop the autolysis and precipitate the pancreatin.
Pancreatin can also be produced by removing water from the comminuted pancreas, by freeze-drying, vacuum drying or the like followed by a fat-extraction step with organic solvents such as acetone. alcohols and ether. The use of acetone for defattening is commonly known (Melcer et al., U.S. Pat. No. 3,168,448; Lewis U.S. Pat. No. 3,956,493). Since the defattening step is not performed on the concentrated pancreatine but rather, on cruder preparations thereof, large quantities of solvents are required. WO 91/07948 of Atzl et al., published Jun. 13, 1991, for example, teaches the use of 4000 liters of acetone for 1000 kg of pancreas pulp.
Traditional methods of pancreatin production also teach the use of large volumes of isopropanol: at a concentration of 10% to 20% (v/p) for autolysis, 20% (v/v) for the extraction step and 80% (v/v) for the precipitation. Since large volumes of pancreas preparations are treated, large quantities of solvent, such as isopropanol, are used.
In view of the problems associated with the management of organic solvents and the costs thereof, there thus remains a need for a method of pancreatin production which minimises the use of organic solvents.
There also remains a need for a method of pancreatin production which enables the obtention of a pancreatin containing less traces of organic solvents than conventionally produced pancreatin preparations.
The present invention seeks to meet these and other needs.
The instant description found herein refers to a number of documents, the content of which is herein incorporated by reference.